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Placental multi-omics integration identifies candidate functional genes for birthweight

Author

Listed:
  • Fasil Tekola-Ayele

    (National Institutes of Health)

  • Xuehuo Zeng

    (National Institutes of Health)

  • Suvo Chatterjee

    (National Institutes of Health)

  • Marion Ouidir

    (National Institutes of Health)

  • Corina Lesseur

    (Icahn School of Medicine at Mount Sinai)

  • Ke Hao

    (Icahn School of Medicine at Mount Sinai)

  • Jia Chen

    (Icahn School of Medicine at Mount Sinai)

  • Markos Tesfaye

    (National Institutes of Health)

  • Carmen J. Marsit

    (Rollins School of Public Health of Emory University)

  • Tsegaselassie Workalemahu

    (University of Utah)

  • Ronald Wapner

    (Columbia University)

Abstract

Abnormal birthweight is associated with increased risk for cardiometabolic diseases in later life. Although the placenta is critical to fetal development and later life health, it has not been integrated into largescale functional genomics initiatives, and mechanisms of birthweight-associated variants identified by genome wide association studies (GWAS) are unclear. The goal of this study is to provide functional mechanistic insight into the causal pathway from a genetic variant to birthweight by integrating placental methylation and gene expression with established GWAS loci for birthweight. We identify placental DNA methylation and gene expression targets for several birthweight GWAS loci. The target genes are broadly enriched in cardiometabolic, immune response, and hormonal pathways. We find that methylation causally influences WNT3A, CTDNEP1, and RANBP2 expression in placenta. Multi-trait colocalization identifies PLEKHA1, FES, CTDNEP1, and PRMT7 as likely functional effector genes. These findings reveal candidate functional pathways that underpin the genetic regulation of birthweight via placental epigenetic and transcriptomic mechanisms. Clinical trial registration; ClinicalTrials.gov, NCT00912132.

Suggested Citation

  • Fasil Tekola-Ayele & Xuehuo Zeng & Suvo Chatterjee & Marion Ouidir & Corina Lesseur & Ke Hao & Jia Chen & Markos Tesfaye & Carmen J. Marsit & Tsegaselassie Workalemahu & Ronald Wapner, 2022. "Placental multi-omics integration identifies candidate functional genes for birthweight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30007-1
    DOI: 10.1038/s41467-022-30007-1
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